Quantification of Amphetamine-Induced Changes in [¹¹C]Raclopride Binding with Continuous Infusion

Abstract

Summar y : Positron emISSIOn tomography and single photon emission computer tomography receptor-binding ligands can be used to measure changes in neurotransmitter levels. In particular, amphetamine-induced dopamine re lease has been assessed with P lC)raclopride by paired bolus injections and with [l 23 I]iodobenzamide by using a single bolus plus infusion (B/I) study. Here, we measured the change in P lC)raclopride-specific binding in rhesus mon keys after 4v. administration of 0.4 mg/kg amphetamine by using both the bolus and B/I paradigms. Paired bolus studies (control and postamphetamine) were analyzed us ing compartment modeling and graphical analysis with a new plasma metabolite model to measure the total distribu tion volume (VT). Specific binding, calculated with threeThe tissue concentration of receptor-binding ra diopharmaceuticals depends on many physiological parameters. A wide variety of approaches have been developed to determine parameters of neuroreceptor binding that are ideally equal or at least linearly pro portional to the free receptor concentration. These techniques include full kinetic modeling with multi ple-parameter estimation, graphical approaches that estimate one or two combined model parameters such as the total volume of distribution (VT) and simple tissue concentration ratios. With such tech niques, within-subject changes in free receptor con centration-for example, caused by an intervention

Long-Term Test–Retest Reliability of Striatal and Extrastriatal Dopamine D2/3 Receptor Binding: Study with [11C]Raclopride and High-Resolution PET

“…RM is considered to be a gold standard in activation-type studies when using a B/I protocol. 30 The validity of both SRTM and RM modeling using B/I of [ 11 C]raclopride has previously been evaluated by Mawlawi et al, 18 and they found SRTM and RM (denoted in their paper as 'equilibrium V3') to yield very similar values. In their test-retest analyses SRTM provided slightly but significantly better reproducibility in the caudate nucleus and putamen and equivalent reproducibility in VST and the thalamus.…”

Nicotine-Induced Dopamine Release in Primates Measured with [11C]Raclopride PET

“…Therefore, perturbations of DA release may alter the apparent BP of the ligand to DA receptors. Several studies have shown the feasibility of this technique and such measurements have been performed with drugs that act directly on the DA system, for example, amphetamine Carson et al, 1997;Dewey et al, 1993) and cocaine (Schlaepfer et al, 1997), and drugs that cause DA release indirectly, for example, ketamine (Breier et al, 1998) or serotonergic agents (Dewey et al, 1995). Such experiments have been conducted in patients with schizophrenia with amphetamine administration Laruelle et al, 1996); amphetamine, however, has the potential to cause short-term exacerbation of psychosis.…”

News and views on in-vivo imaging of neurotransmission using PET and MRI

“…To increase the sensitivity to changes in receptor availability experimentally for any tracer, bolus plus infusion injections can be used. This has been shown first for [ 11 C]raclopride 54 and in addition can simplify quantification of radiotracer binding. Infusion injections can even be applied to irreversibly binding radiotracers like [ 18 F]FDG 119 .…”

“…Perhaps the most commonly investigated stimulant is amphetamine due to its potency. Studies with amphetamine have demonstrated significant decreases (>20% occupancy) in D2/D3 receptor availability in the striatum and in the cortex 54–57 . It has been shown that these decreases are directly correlated to dopamine release timing and magnitude both in striatal and cortical regions 58,59 .…”